Second-generation Atypical Antipsychotics Research Articles

An analysis of multiple comparisons is conducted to account for correlations among various investigated variables across four categories of antipsychotics

Background: First-generation antipsychotics are dopamine receptor antagonists, while second-generation atypical antipsychotics are serotonin-dopamine antagonists. Aim: The study aims to compare the effectiveness of current anti-psychotic drugs in treating schizophrenia, focusing on their correlation with responsiveness rates in positive, negative, and psychopathological symptoms. Methods: The study focuses on schizophrenia-spectrum disorders in adults and elderly psychiatric patients at the Princess Aisha Bint Al Hussein Medical Centre. The study will assess the initial severity of patients and evaluate the therapeutic effectiveness of four categorical-based oral and LA-APDs: older oral drugs, older oral and depot drugs, newer oral drugs, and newer oral and depot drugs. The reduction percentages in each component will be monitored, and a Chi Square test will be performed to analyze other variables. Pearson or spearman correlations will be used to explore correlation values. Results: Upon aggregating the various symptom categories into a unified score using the Positive and Negative Scoring Scale (PANSS), this study revealed that 63.7% of patients exhibited a positive response, whereas 36.7% of patients did not respond favourably. This equated to 110 out of 303 patients responding, compared to 193 patients who did not respond. The Pearson and Spearman correlations exhibited a statistically significant positive relationship, with values of +0.581±0.038 and +0.574±0.040, respectively (χ 2=131.885, p-value=0.000). Conclusion: Our study concluded that Psychopathological symptom therapy and patient adherence improved significantly. The efficiency of pleasant symptoms decreased significantly, whereas negative symptoms increased slightly.

Risk of Poor Neonatal Adaptation Syndrome Among Infants Exposed to Second-Generation Atypical Antipsychotics Compared to Antidepressants: Results From the National Pregnancy Registry for Psychiatric Medications.

Objective: While poor neonatal adaptation syndrome (PNAS) has been particularly well described among infants exposed to antidepressants, specifically selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), this is not the case for second-generation antipsychotics (SGAs). In 2011, the US Food and Drug Administration (FDA) issued a drug safety warning regarding fetal antipsychotic exposure and risk for PNAS and extrapyramidal symptoms (EPS). The primary objective of this study was to examine the risk for PNAS among infants exposed to SGAs compared to SSRI/SNRI-exposed infants, leveraging the prospective, longitudinal design of the National Pregnancy Registry for Psychiatric Medications (NPRPM). Methods: The NPRPM is a prospective pharmacovigilance program in which pregnant women, aged 18–45 years, are enrolled and followed prospectively. Medical records were systematically reviewed and data abstracted using a checklist of PNAS and EPS symptoms specifically outlined in the FDA drug safety warning. The two study groups included infants exposed to an SGA during pregnancy and infants exposed to an SSRI/SNRI during pregnancy. The primary outcome was the presence of at least one or more PNAS symptoms during the first month of life. Other neonatal outcomes following exposure to the medication of interest, including preterm birth, neonatal intensive care unit (NICU) admission, rates of EPS, and whether infants were discharged home with their mothers, are also reported. Results: Of the 2,145 women enrolled in this study as of December 16, 2020, a total of 373 women and their infants (n = 384) were eligible for inclusion (n = 193 SGA-exposed infants and 191 SSRI/SNRI-exposed infants). Among SGA-exposed infants, 32.6% (63/193) experienced at least 1 PNAS sign compared to 34.6% of infants (66/191) in the SSRI/SNRI-exposed group. The majority of infants in each group showed no symptoms of PNAS. No differences were observed between the two groups with respect to rates of preterm birth, NICU admission, prevalence of EPS, and timing of infants being discharged home with their mothers. Conclusions: PNAS symptomatology was comparable among infants exposed prenatally to an SGA or to an SSRI/SNRI. These preliminary findings provide an estimated risk of PNAS among infants exposed to SGAs of roughly 30%. Interestingly, these findings are also consistent with estimates in the literature of PNAS in SSRI/SNRI-exposed infants, suggesting a possible common pathway underlying this phenomenon. Trial Registration: ClinicalTrials.gov identifier: NCT01246765

Accumulation of Reproductive Safety Data for Second-Generation Atypical Antipsychotics: A Call to Accelerate the Process.

This commentary on an article by Yakuwa and colleagues calls for an acceleration of the acquisition of clinical data on the safety of second-generation antipsychotics for pregnant women and their infants.

Prevalence and Management of Metabolic Syndrome in Adult Psychiatric Patients Receiving Second-Generation Antipsychotics at Sheikh Khalifa Medical City.

IntroductionThe establishment of second-generation antipsychotics in the early 1900s has shown greater benefits in many outcome domains. As atypical antipsychotics revealed an improvement in the shortcomings of first-generation antipsychotics, they also have significant limitations in terms of side effects.BackgroundAs a class, atypical antipsychotics have a more satisfactory profile in terms of extrapyramidal side effects but have other side effects, including metabolic syndrome. Moreover, a patient with severe mental illness has reduced life expectancy compared to the general population and increased dying risk by two to three folds due to the associated risk of metabolic syndrome. Metabolic syndrome induced by second-generation antipsychotics requires routine monitoring, suitable intervention, and management, including lifestyle modification, caregiver education, and the use of other medications like lipid-lowering agents, anti-diabetics, and adjunctive therapies.MethodThis is a retrospective observational study that involves a review of medical records of adult patients attending the psychiatry outpatient clinics in Shaikh Khalifa Medical City to whom oral second-generation atypical antipsychotics were prescribed between January 2016 and December 2017. All pediatric patients were excluded, as well as those who are on other agents known to induce metabolic syndrome, including first-generation antipsychotics, mood stabilizers, anxiolytics, and anti-depressants. Besides, a patient who already developed metabolic syndrome before starting atypical antipsychotics was excluded as well. IBM SPSS v. 25 (IBM Corp., Armonk, NY) and Jamovi 1.0.4.0 (The jamovi project (2021). [Computer Software]. Retrieved from https://www.jamovi.org) were used for statistical analysis. The Shapiro-Wilk was used to test for normality of data, One-way repeated measure analysis of variance (ANOVA) was used to determine whether there are any statistically significant differences between the means of BMI across the three pre-specified time points, Kendall’s tau was used to test the correlation between categorical variables, and the paired t-test was used to determine whether there was a statistically significant mean difference between BMI at baseline and after one year, a p-value above 0.05 is considered non-significant.ResultA total of 123 patients were included in this study out of 4123 patients. An olanzapine disintegrating tablet was the most used atypical antipsychotic among the study population, followed by risperidone and quetiapine, respectively. Furthermore, BMI was statistically significantly increased from baseline to six months (M = 2.37 kg/m2, p = .002), and from baseline to 12 months (M =3.26 kg/m2, p < .001) but not from six months to 12 months (M =1.41 kg/m2, p = .346). Due to lack of documentation and monitoring, it was difficult to assess the continuous change in total cholesterol level/high-density lipoprotein, glucose, and HbA1C level. It was observed that nine (7.32%) patients of those who have been included in the study started a treatment to manage the metabolic syndrome.ConclusionPatients on second-generation antipsychotics must be monitored and treated in case of metabolic syndrome development to decrease the high risk of mortality in such patients. Documentation of such complications, patient treatment, and progress is essential for outcome improvement.

Management of psychiatric disorders in patients with cancer.

Management of psychiatric disorders in patients with cancer.

61-Year-Old Man With Nausea and Vomiting

61-Year-Old Man With Nausea and Vomiting

Comparative Characteristics of the Metabolic Syndrome Prevalence in Patients With Schizophrenia in Three Western Siberia Psychiatric Hospitals.

Objective: The purpose of this study was to compare the prevalence of MetS and the associated sociodemographic, clinical, and pharmacotherapeutic characteristics of patients with schizophrenia in three psychiatric hospitals in the West Siberian region.Methods: Patients with a clinical diagnosis of schizophrenia (ICD-10: F20) and an age between 18 and 60 years were included in the study after giving informed consent. Metabolic syndrome was diagnosed according to the International Diabetes Federation criteria. This research was carried out at three Western Siberian psychiatric hospitals in Kemerovo, Tomsk, and Omsk. The study population included respectively 94, 131, and 91 inpatients with schizophrenia. We carried out schizophrenia symptoms assessment by PANSS, antipsychotic therapy evaluation, anthropometry, and biochemical analysis. Statistical Analysis included the Shapiro–Wilk test, non-parametric Kruskal–Wallis H-test for independent samples, Mann–Whitney U-test for independent samples, the chi-square test, stepwise multiple regression analyses. The level of significance was p < 0.05.Results: The metabolic syndrome prevalence was higher among patients in Tomsk (36.6%), compared with Kemerovo (20.2%, p = 0.008) or Omsk (18.7%, p = 0.004), mainly due to the high prevalence of abdominal obesity, while men from Tomsk were more susceptible to this condition than men from other regions (p < 0.05). Patients from Omsk had the highest severity schizophrenia symptoms according to PANSS, and patients from Tomsk had the lowest severity of positive symptoms according to PANSS. Patients from Tomsk had the minimum duration of antipsychotic therapy compared with the patient from Kemerovo (p = 0.017) and from Omsk (p = 0.000019), but most patients from Tomsk received second-generation atypical antipsychotics, while patients from Omsk received mainly conventional antipsychotics (p = 0.0001). Multiple regression analysis showed that metabolic syndrome associated with schizophrenia duration and body mass index, although the association was not so strong (adjusted R2 = 0.2435, p < 0.0001).Discussion: The study illustrates that in different psychiatric hospitals within the same region, the prevalence of metabolic syndrome in patients with schizophrenia can vary significantly, which dictates the need to look for opportunities to minimize the risk of its occurrence, taking into account the experience of each hospital.

Clozapine Worsens Glucose Intolerance, Nonalcoholic Fatty Liver Disease, Kidney Damage, and Retinal Injury and Increases Renal Reactive Oxygen Species Production and Chromium Loss in Obese Mice.

Clozapine is widely employed in the treatment of schizophrenia. Compared with that of atypical first-generation antipsychotics, atypical second-generation antipsychotics such as clozapine have less severe side effects and may positively affect obesity and blood glucose level. However, no systematic study of clozapine’s adverse metabolic effects—such as changes in kidney and liver function, body weight, glucose and triglyceride levels, and retinopathy—was conducted. This research investigated how clozapine affects weight, the bodily distribution of chromium, liver damage, fatty liver scores, glucose homeostasis, renal impairment, and retinopathy in mice fed a high fat diet (HFD). We discovered that obese mice treated with clozapine gained more weight and had greater kidney, liver, and retroperitoneal and epididymal fat pad masses; higher daily food efficiency; higher serum or hepatic triglyceride, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and creatinine levels; and higher hepatic lipid regulation marker expression than did the HFD-fed control mice. Furthermore, the clozapine group mice exhibited insulin resistance, poorer insulin sensitivity, greater glucose intolerance, and less Akt phosphorylation; their GLUT4 expression was lower, they had renal damage, more reactive oxygen species, and IL-1 expression, and, finally, their levels of antioxidative enzymes (superoxide dismutase, glutathione peroxidase, and catalase) were lower. Moreover, clozapine reduced the thickness of retinal cell layers and increased iNOS and NF-κB expression; a net negative chromium balance occurred because more chromium was excreted through urine, and this influenced chromium mobilization, which did not help overcome the hyperglycemia. Our clozapine group had considerably higher fatty liver scores, which was supported by the findings of lowered adiponectin protein levels and increased FASN protein, PNPLA3 protein, FABP4 mRNA, and SREBP1 mRNA levels. We conclude that clozapine can worsen nonalcoholic fatty liver disease, diabetes, and kidney and retinal injury. Therefore, long-term administration of clozapine warrants higher attention.

Severe Tachycardia Associated with Psychotropic Medications in Psychiatric Inpatients: A Study of Hospital Medical Emergency Team Activation.

The use of antipsychotic medications is associated with side effects, but the occurrence of severe tachycardia (heart rate ≥ 130 per minute) is not well described. The aim of this study was to determine the frequency and strength of the association between antipsychotic use and severe tachycardia in an inpatient population of patients with mental illness, while considering factors which may contribute to tachycardia. We retrospectively analyzed data from 636 Medical Emergency Team (MET) calls occurring in 449 psychiatry inpatients in three metropolitan hospitals co-located with acute medical services, and used mixed-effects logistic regression to model the association between severe tachycardia and antipsychotic use. The median age of patients was 42 years and 39% had a diagnosis of schizophrenia or psychotic disorder. Among patients who experienced MET calls, the use of second-generation (atypical) antipsychotics was commonly encountered (70%), but the use of first-generation (conventional) antipsychotics was less prevalent (10%). Severe tachycardia was noted in 22% of all MET calls, and sinus tachycardia was the commonest cardiac rhythm. After adjusting for age, anticholinergic medication use, temperature >38 °C and hypoglycemia, and excluding patients with infection and venous thromboembolism, the odds ratio for severe tachycardia with antipsychotic medication use was 4.09 (95% CI: 1.64 to 10.2).

Initial assessment of an interprofessional team-delivered telehealth program for patients with epilepsy

IntroductionEpilepsy affects 3.5 million people in the United States (US). Rural-dwelling individuals have less access to healthcare and consequently poorer health outcomes. This study describes the outcomes of an interprofessional telehealth program for rural-dwelling individuals with epilepsy in one US state. MethodsAn academic medication therapy management pharmacist provided clinical services to rural-dwelling individuals with epilepsy between November 2015 and June 2018, using video-conferencing technology and follow-up telephonic consultation. Data collected included: demographics, prescribed seizure medications, comorbidities, drug-drug and drug-disease interactions, adverse drug reactions, therapeutic duplications, dose-related safety concerns, adherence concerns, and recommendations to resolve identified issues. Data were summarized using appropriate descriptive statistics. ResultsA total of 168 patients (51% male, mean age 28 ± 15 years), participated in this pilot study. Most participants (94%) were prescribed at least one seizure medication including: benzodiazepines (n = 89), lamotrigine (n = 58), and levetiracetam (n = 56). The majority (55%) had at least one comorbidity including: mood disorders (n = 49) and psychiatric disorders (n = 26). Common medications with reported precautions for people with a seizure history were: selective serotonin reuptake inhibitors (n = 18), second-generation atypical antipsychotics (n = 17) and benzodiazepines (n = 16). Participants had at least one: drug-disease interaction (33%), drug-drug interaction (54%), adverse drug reaction (37%), therapeutic duplication (13%); dose-related safety concerns (35%); and medication utilization concerns (13%). DiscussionThis pharmacist-delivered pilot program was effective in: reaching underserved patients with epilepsy, identifying and recommending resolutions to medication-related problems, and demonstrating the value of pharmacists in an interprofessional team. Further work is warranted to identify telehealth strategies to reduce medication associated problems.

Reversibility of psychotropic medication induced weight gain among children and adolescents with bipolar disorders

ObjectiveTo assess the reversibility of weight gain associated with psychotropic medications in children. MethodsA retrospective cohort study was conducted using an ambulatory electronic medical records database. Individuals under 18 years of age were identified if they were initiating a new course of second generation/atypical antipsychotics (SGA) or mood stabilizers (MS) following a bipolar disorder diagnosis and subsequently discontinued treatment within 24 months of treatment initiation. ResultsOf the 297 children who had experienced positive BMI percentile increase (mean±SD: 8.71±11.94) during the treatment of SGA and/or MS, treatment discontinuation led to an average of 1.88 (±13.41) unit decrease in BMI percentile during a 12-month period since the treatment discontinuation. Repeated measure mixed model analysis showed that the reduction of BMI percentile after treatment discontinuation was neither associated with the treatment regimens patients previously received, nor associated with time since the treatment discontinuation. The three statistically significant predictors were baseline BMI percentile, BMI percentile gained during the treatment, and comorbid substance abuse disorder. ConclusionChildren with bipolar disorder were able to lose a fraction of weight gained during pharmacotherapy after the treatment discontinuation, however, their BMI percentile may not return to the prior treatment level within a year post-medication discontinuation.

Second generation atypical antipsychotics olanzapine and aripiprazole reduce expression and secretion of inflammatory cytokines in human immune cells

Schizophrenia and major depression are associated with alterations in peripheral inflammatory markers, and anti-inflammatory therapy has been proposed as a promising add-on approach in the pharmacologic treatment of both disorders. Second-generation atypical antipsychotics are currently first-line drugs in the treatment of schizophrenia and are also used as augmentation strategies in treatment-resistant major depression. Furthermore, these drugs have been reported to exhibit distinct metabolic side effects and to influence inflammatory processes.In this study, we used ex vivo stimulation of primary human peripheral blood mononuclear cells (PBMC) from healthy blood donors with atypical antipsychotics olanzapine or aripiprazole to examine effects on cytokine production independent from metabolic side effects and disease status.Both olanzapine and aripiprazole stimulation decreased mRNA levels of IL-1β, IL-6, and TNF-α and resulted in diminished protein concentrations of IL-6 and TNF-α in conditioned medium of stimulated PBMC. A multiplex approach revealed additional downregulation of IL-2; MIP-1β and IP-10 secretion. Similarly, olanzapine and aripiprazole stimulation of the human monocytic cell line THP-1 resulted in a significant decrease in expression and secretion of IL-1β and TNF-α. Our results suggest that atypical antipsychotics directly influence immune cell function and thereby highlight the importance to factor in potential side effects of drugs routinely used in treatment of schizophrenia and major depression on inflammatory processes when considering anti-inflammatory drug therapy as an additional treatment option.

Effect of melatonin in reducing second-generation antipsychotic metabolic effects: A double blind controlled clinical trial

IntroductionThe use of second-generation atypical antipsychotics has an increasing role in the development of metabolic syndrome. However, these medications due to metabolic disorders can lead to an increased risk of cardiovascular disease and subsequently mortality as well as reduced adherence to treatment. The main objective of current study was to determine the ability of melatonin to reduce the metabolic effects of second-generation antipsychotics. MethodsThis double blind controlled clinical trial was conducted on 100 patients aged 18–64 years old were treated with the second-generation antipsychotics for the first time. The patients were divided randomly into two groups of 50. The case group received slow-release melatonin at a dose of 3mg and the control group was given oral placebo at 8 p.m. ResultsThe findings in melatonin group indicated significantly increase of HDL and decreased fasting blood sugar and systolic blood pressure, as well as had statistically significant increase in waist circumference, weight and BMI compared with placebo group. ConclusionAccording to the findings, it can be claimed that the addition of melatonin to atypical antipsychotics has led to a reduction in some of the metabolic effects of these drugs. In this study, HDL level was increased, and the mean systolic blood pressure and FBS were decreased in the melatonin group. Considering that these factors are contributing to cardiovascular disease as a leading cause of mortality in psychiatric patients, so the use of melatonin can reduce some of the medical effects of long-term treatment of atypical antipsychotics.

Atypical antipsychotics: recent research findings and applications to clinical practice: Proceedings of a symposium presented at the 29th Annual European College of Neuropsychopharmacology Congress, 19 September 2016, Vienna, Austria.

Available evidence suggests that second-generation atypical antipsychotics are broadly similar to first-generation agents in terms of their efficacy, but may have a more favourable tolerability profile, primarily by being less likely to cause extrapyramidal symptoms. However, atypical antipsychotics are variably associated with disturbances in the cardiometabolic arena, including increased body weight and the development of metabolic syndrome, which may reflect differences in their receptor binding profiles. Effective management of schizophrenia must ensure that the physical health of patients is addressed together with their mental health. This should therefore involve consideration of the specific tolerability profiles of available agents and individualization of treatment to minimize the likelihood of adverse metabolic sequelae, thereby improving long-term adherence and optimizing overall treatment outcomes. Alongside this, modifiable risk factors (such as exercise, diet, obesity/body weight and smoking status) must be addressed, in order to optimize patients' overall health and quality of life (QoL). In addition to antipsychotic-induced side effects, the clinical management of early nonresponders and psychopharmacological approaches for patients with treatment-resistant schizophrenia remain important unmet needs. Evidence suggests that antipsychotic response starts early in the course of treatment and that early nonresponse accurately predicts nonresponse over the longer term. Early nonresponse therefore represents an important modifiable risk factor for poor efficacy and effectiveness outcomes, since switching or augmenting antipsychotic treatment in patients showing early nonresponse has been shown to improve the likelihood of subsequent treatment outcomes. Recent evidence has also demonstrated that patients showing early nonresponse to treatment with lurasidone at 2 weeks may benefit from an increase in dose at this timepoint without compromising tolerability/safety. However, further research is required to determine whether these findings are generalizable to other antipsychotic agents.

Quetiapine misuse and abuse: Is it an atypical paradigm of drug seeking behavior?

Recent case reports in medical literatures suggest that more and more second-generation atypical antipsychotics (AAs) have been prescribed for off-label use; quetiapine (Brand name: Seroquel®) showed increase in its trend for off-label use. Little is known about the reasons behind this trend, although historical sedative and hypnotic prescription patterns suggest that despite relatively superior safety profiles of quetiapine (especially for movement disorders), it may be used for treating substance abuse disorder. In addition, recent studies have shown a strong potential for misuse and abuse (MUA) of quetiapine beyond Food and Drug Administration-approved indications. This includes drug-seeking behaviors, such as feigning symptoms, motivated by quetiapine and use of quetiapine in conjunction with alcohol. Quetiapine appears to be the most documented AA with street values bartered illicitly on the street. A recent report from the Drug Abuse Warning Network has shown a high prevalence of quetiapine-related emergency department visits involving MUA. Several other case studies have found that quetiapine causes seeking behaviors observed in substance use disorder. In fact, the majority of quetiapine MUA involved patients diagnosed with substance use disorder. In the absence of a definitive mechanism of action of quetiapine's reinforcing properties, it is imperative to gather robust evidence to support or refute increasing off-label use of AAs.

Screening for diabetes in patients receiving second-generation atypical antipsychotics.

Results of a study to assess adherence with a consensus statement for diabetes screening in patients receiving atypical antipsychotics and to evaluate the role of pharmacists in a patient-centered medical home in improving guideline adherence are presented. For patients prescribed atypical antipsychotics, records were reviewed for glycosylated hemoglobin (HbA1c) testing within the past 12 months. If no HbA1c results were found within that time frame, physicians were sent an alert in the patient's electronic medical record requesting an HbA1c order. Patient medical records were reviewed to analyze the number of HbA1c orders before and after pharmacist intervention. Prior to pharmacist intervention, 17 of 120 (14%) patients were screened with HbA1c. As a result of pharmacist intervention, 86 alerts were sent to physicians to order an HbA1c level, 24 (28%) of which included an order for an HbA1c level. Eleven of 24 (46%) HbA1c test results were collected during study follow-up, and one prediabetic patient was identified. After pharmacist intervention, a greater number of patients receiving atypical antipsychotic medications had HbA1c levels monitored for evidence of type 2 diabetes.

Enhanced Degradation of Lactide-co-Glycolide Polymer with Basic Nucleophilic Drugs

The purpose of this study was to examine the degradative effect of weakly basic nucleophilic drugs on a lactide-co-glycolide (PLGA) polymer in a microsphere formulation. Biodegradable PLGA microspheres of two second-generation atypical antipsychotics, Risperidone and Olanzapine, were manufactured using a solvent extraction/evaporation technique. The effect of drug content, buffer pH and temperature on polymer molecular weight and degradation, were examined via a series of experiments and compared against a control (Placebo PLGA microspheres). In comparison to Placebo microspheres, significant polymer molecular weight reduction was observed upon encapsulation of varying levels of either Risperidone or Olanzapine. There was excellent correlation between the extent of molecular weight reduction during manufacture and the amount of encapsulated drug in the microspheres. Subsequent studies on polymer degradation showed: the following (a) the Placebo and Olanzapine microspheres followed pseudo first order kinetics, (b) Risperidone microspheres exhibited biphasic degradation profiles, and (c) polymer degradation was dependent on temperature, not pH. The findings of these studies show that encapsulation of weakly basic nucleophile type drugs into PLGA can accelerate the biodegradation of the PLGA and have major implications on the design of polymeric microsphere drug delivery systems.

A Review of the Role of Antipsychotics as an Augmentation Agent or Treatment Option for Patients with Treatment Resistant Unipolar Depression

Background: Patients with unipolar depression present a unique challenge for physicians who are considering therapeutic drug treatment. Physicians have historically treated patients who present symptoms of unipolar depression with SSRIs or other medications that are commonly prescribed to patients with non-unipolar depression. Many of these medications are ineffective for patients suffering from unipolar disorder. Recently, an exciting new treatment approach for the depressive symptoms related to unipolar disorder has emerged in the form of secondgeneration atypical antipsychotics. A wealth of empirical support for treating treatment-resistant bipolar depression is becoming increasingly available, but much less is understood regarding the efficacy of atypical psychotics in treating unipolar depression. Methods: An electronic literature review was conducted through PubMed, PsycINFO, the Cochrane Library, Web of Science, and Embase using the following search phrases: depression, unipolar depression, antipsychotics, second-generation antipsychotics, atypical antipsychotics, and depression treatment. There were no restrictions on publication year, type, or language. Meta-analyses and randomized clinical trials (RCTs) were considered. A sensitivity analysis was performed by excluding studies with small sample sizes and a high placebo effect. Discussion: Preliminary evidence for this treatment approach is promising, although additional clinical trials which more clearly elucidate the role of second-generation atypical antipsychotics in treating unipolar depressive symptoms may be warranted. Accordingly, this article discusses the second-generation atypical antipsychotics that have, to date, received empirical support for use in treating patients with unipolar disorder. Proposed mechanisms of action are discussed and current FDA approvals as well as approval status in different countries for usage are reviewed. Indications for future research are also proposed.

With War-Related Post Traumatic Stress Disorder Being Resistant to Pharmaceuticals is it Time to Give Stellate Ganglion Block (SGB) a Shot?

A large number of war veterans have PTSD in US military punctuated by a very high suicide rate of 22 per veterans per day. Current VA gold standard” treatments protocols will effectively reach no more than 20% of all veterans needing PTSD treatment. A recent study reported results multi- center study on off-label use of second-generation (atypical) antipsychotics has gained wide popularity Risperidone and demonstrated no benefit over placebo for military- related PTSD. This leaves practitioners with few weapons in their pharmacotherapeutic arsenal. The risks of SGA’s are significant, such as sudden heart failure and increase the risk of suicidal attempts, pharmaceutical approach may be moving away from this conventional path. New techniques include modulation of the sympathetic nervous system (SNS) which is a part of the autonomic nervous system. It turns out that a possible treatment of physiologic hyper arousal is available by utilizing minimally invasive modulation of sympathetic nervous system. It seems possible to have similar results by using a common anesthetic procedure called Stellate ganglion Block ( SGB) which is much less invasive. Early results of this new approach are very promising, with a success rate of 70 to 75% a very high compliance, acceptance and minimal risk. Considering severity of PTSD and the lack of effective therapeutic interventions available it is time to dispense with established scientific /medical opinions look at the available data and apply SGB to the population most at risk of PTSD related complications.

Comparative assessment of adherence measures and resource use in SSRI/SNRI-treated patients with depression using second-generation antipsychotics or L-methylfolate as adjunctive therapy.

Antidepressant monotherapy is effective in achieving treatment remission in only approximately one third of patients with depression, and even switching to a second antidepressant brings the cumulative remission rate to only 50%-55%. This has led to an interest in augmentation therapy for the management of treatment-resistant depression. To assess (a) selective serotonin reuptake inhibitor/selective norepinephrine reuptake inhibitor (SSRI/SNRI) adherence when augmented with second-generation atypical antipsychotics (SGAs) or L-methylfolate using a modified application of the Healthcare Effectiveness Data and Information Set (HEDIS) acute medication management (AMM) measures at the time of augmentation, and (b) the depression-specific and total health care cost, comparing the 2 forms of augmentation therapy in the treatment of depressive disorder. Patients with a diagnosis of depression and a pharmacy claim for an SSRI/SNRI between January 1, 2006, and December 31, 2009 (index date), and receiving concomitant augmentation therapy with either an SGA or L-methylfolate (augmentation date), were identified in the MarketScan database and followed for 231 days (follow-up). Patients were excluded for having any pharmacy claim for an antidepressant or SGA 90 days pre-index; having an L-methylfolate claim 6 months pre-index; age < 18 years on the index date; or a diagnosis of pregnancy, dementia, psychotic-related mental disorders, Alzheimer's disease, or Parkinson's disease in the 12-month pre-index period. Propensity score matching (3:1 ratio, atypical antipsychotic to L-methylfolate) was used to select the final study cohorts, using covariates of age, gender, comorbidities, index SSRI/SNRI, and index SSRI/SNRI dose. Adherence to antidepressant therapy was measured from the augmentation date and included a modified application of the HEDIS (mHEDIS) AMM acute and chronic phase measures as well as the 6-month medication possession ratio. Health care utilization and cost were measured for the 6-month postaugmentation period and included both total as well as depression-related utilization/cost. Comparisons between the closely matched SGA and L-methylfolate-augmented cohorts were made using chi-square tests for binary measures and t-tests for continuous measures. Following propensity score matching, 4,053 SGA and 1,351 L-methylfolate patients were found to have augmentation of the index SSRI/SNRI within 12 months of the index date. The comparison groups were well matched on age, gender, comorbidities, and the type and dose of the SSRI/SNRI being augmented. The most common antidepressants augmented in both groups were escitalopram, duloxetine, and venlafaxine. Mean (standard deviation [SD]) time from index to augmentation was 73.5 [96.7] days for SGA and 105.9 [108.7] days for L-methylfolate (P < 0.001). The most common SGAs utilized for augmentation were quetiapine, aripiprazole, and risperidone. L-methylfolate was primarily dosed at 7.5 mg/day. The mHEDIS AMM acute phase measure was met by 68.7% of the SGA cohort and 78.7% of the L-methylfolate cohort (P < 0.001). The mHEDIS continuation phase measure was met by 50.3% of the SGA cohort and 62.1% of the L-methylfolate cohort (P < 0.001) following augmentation. Medical utilization (inpatient, emergency department, and outpatient) was significantly higher for the SGA group, while total prescription utilization was significantly higher in the L-methylfolate group. Mean [SD] total 6-month postaugmentation costs for the SGA group was $8,499 [$13,585] and $7,371 [$12,404] for the L-methylfolate group (P = 0.005), and 6-month depression-related costs were $2,688 [$4,201] for the SGA group and $1,613 [$2,315] for the L-methylfolate group (P < 0.001). Patients who augmented SSRI/SNRI therapy with SGA or L-methylfolate achieved mHEDIS AMM acute phase and continuation phase adherence scores of 69%-79% and 50%-62%, respectively. These modified scores exceeded the 2012 national median benchmarks for unmodified HEDIS AMM measures for commercial health plans. In this study, augmentation with L-methylfolate was associated with significantly higher adherence measures compared with augmentation with SGA. In addition, health care utilization and total health care costs, as well as depression-related costs, were significantly lower in the L-methylfolate augmentation group compared with augmentation with SGA.